CA-GILEAD-SCIENCES,-INC.

Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the company’s
Marketing Authorization Application (MAA) for tenofovir alafenamide (as
fumarate) (TAF) 25 mg – an investigational, once-daily treatment for
adults with chronic hepatitis B virus (HBV) infection – has been fully
validated and is now under assessment by the European Medicines Agency
(EMA).

TAF is a novel, targeted prodrug of tenofovir that has demonstrated high
antiviral efficacy similar to Gilead’s Viread®
245 mg of
tenofovir disoproxil (as fumarate) (TDF) at one-tenth of the dose. TAF
also demonstrated improvements in surrogate laboratory markers of renal
and bone safety compared to TDF in clinical trials.

“Chronic hepatitis B infection is a major health concern in Europe, with
14 million people living with the disease and more than 1 million
Europeans newly infected with the virus each year,” said Norbert
Bischofberger, PhD, Executive Vice President, Research and Development
and Chief Scientific Officer, Gilead Sciences. “The validation of this
application represents the latest step in our continued efforts to
advance the care of people living with progressive liver diseases like
HBV.”

The MAA for TAF is supported by 48-week data from two Phase 3 studies
which met their primary objective of non-inferiority in efficacy (HBV
DNA < 29 IU/mL at week 48)
compared to TDF among
treatment-naïve and treatment-experienced adults with HBeAg-negative and
HBeAg-positive chronic HBV. In both studies, treatment with TAF showed a
statistically significant increase in serum alanine aminotransferase
normalization relative to the TDF arms when using the American
Association for the Study of Liver Disease criteria. Changes in renal
and bone laboratory safety parameters favored the TAF treatment regimen.
Overall, patients receiving TAF experienced a significantly smaller mean
percentage decrease from baseline in hip and spine bone mineral density
at week 48 compared to patients receiving TDF. Additionally, the overall
median change in serum creatinine from baseline to week 48 favored TAF.
Rates of discontinuations due to adverse events and the most commonly
reported adverse events were similar in patients receiving TAF or TDF.

TAF for the treatment of HBV will be reviewed by the EMA under the
centralized licensing procedure which, if authorized, provides marketing
authorization in all 28 member states of the European Union, Norway and
Iceland. Gilead also submitted a New Drug Application to the U.S. Food
and Drug Administration (FDA) for TAF on January 11, 2016.

TAF as a single agent treatment for HBV is an investigational product
and its safety and efficacy have not been established.

Important Safety Information About Viread

Please refer to the Viread individual Summary of Product
Characteristics for full prescribing information

Adults: One tablet (245 mg) once daily taken with food. Viread is
available as 33 mg/g granules for the treatment of CHB in adults for
whom a solid dosage form is not appropriate. No dose modification is
necessary in patients with mild to moderate liver disease. Optimal
duration of treatment is unknown. Children and adolescents: for the
treatment of CHB in adolescents aged 12 to < 18 years and weighing ≥ 35
kg, recommended dose is one tablet (245 mg) once daily taken with food.
The safety and efficacy of Viread in children with CHB aged 2 to < 12
years or weighing < 35 kg have not been established. Viread is also
available as 33 mg/g granules for the treatment of CHB in adolescents
aged 12 to < 18 years for whom a solid dosage form is not appropriate.
Not recommended in paediatric patients with renal impairment. No dose
adjustment is required in patients with hepatic impairment. Elderly:
Insufficient data are available on which to make dose recommendations
for patients over the age of 65 years – caution should be exercised.

Contraindications:

Known hypersensitivity to tenofovir, tenofovir disoproxil fumarate, or
any of the excipients.

Warnings and Precautions:

Renal:
If Viread is co-administered with a non-steroidal
anti-inflammatory drug (NSAID), renal function should be monitored
adequately. A higher risk of renal impairment has been reported in
patients receiving Viread in combination with a ritonavir or cobicistat
boosted protease inhibitor. A close monitoring of renal function is
required in these patients. Renal failure and impairment, elevated
creatinine, hypophosphataemia and proximal tubulopathy (including
Fanconi syndrome) have been reported with the use of Viread in clinical
practice. It is recommended that creatinine clearance (CrCl) is
calculated in all patients prior to therapy initiation and renal
function monitored after two to four weeks of treatment, after three
months of treatment and every three to six months thereafter in patients
without renal risk factors. In patients at risk of renal impairment, a
more frequent monitoring of renal function is required. There are
limited data on the safety and efficacy of Viread in adult patients with
impaired renal function. Viread should only be used in these patients if
the potential benefits outweigh the risks. Interrupting treatment with
Viread should be considered in case of progressive decline of renal
function when no other cause has been identified. For adult patients
with moderate (CrCl < 30-49 ml/min) or severe (CrCl < 30 ml/min) renal
impairment including haemodialysis patients, daily dose adjustment using
Viread 33 mg/g granules is recommended. For adult patients with moderate
and severe renal impairment who are unable to use the granules
formulation, and with no alternative treatments available, prolonged
dose intervals using Viread 245 mg film-coated tablets may be used.
Viread is not recommended in paediatric patients with renal impairment.
Viread should be discontinued in paediatric patients who develop renal
impairment during therapy.

Exacerbations of Hepatitis:
Flares on treatment:
Spontaneous exacerbations in CHB are relatively common. Patients with
cirrhosis may be at higher risk for hepatic exacerbations and therefore
should be monitored closely. However it also should be noted that
increase in ALT can be part of HBV clearance during therapy with Viread.
Flares after treatment discontinuation: Acute exacerbations of hepatitis
have also been reported in patients who have discontinued hepatitis B
therapy. Hepatic function should be monitored at repeated intervals with
both clinical and laboratory follow-up for at least 6 months after
discontinuation of therapy. Treatment discontinuation is not recommended
in patients with advanced liver disease or cirrhosis, since
post-treatment exacerbations of hepatitis may lead to hepatic
decompensation.

Hepatic Decompensation:
There are limited data on the
safety and efficacy of Viread in HBV-infected patients with
decompensated liver disease and who have a Child Pugh Turcotte (CPT)
score > 9. These patients may be at higher risk of experiencing serious
hepatic or renal adverse reactions. Therefore, hepatobiliary and renal
parameters should be closely monitored in this patient population.

Hepatic Disease:
Safety and efficacy data are very limited
in liver transplant patients.

Bone:
Viread may cause a reduction in bone mineral density
(BMD). The effects of Viread-associated changes in BMD on long term bone
health and future fracture risk are unknown. If bone abnormalities are
detected/suspected in paediatric patients, consult an endocrinologist
and/or nephrologist. Bone abnormalities (infrequently contributing to
fractures) may be associated with proximal renal tubulopathy.

HIV Co-infection:
HIV antibody testing should be offered
to all CHB patients before initiating Viread therapy. Due to the risk of
development of HIV resistance, Viread should only be used as part of an
appropriate antiretroviral combination regimen in HIV/hepatitis B virus
(HBV) co-infected patients. Patients must be advised Viread has not been
proven to prevent the risk of transmission of HIV or HBV to others
through sexual contact or contamination with blood and appropriate
precautions must be used.

Co-infection with Hepatitis C or D:
There are no data on
the efficacy of Viread in patients co-infected with hepatitis C or D
virus.

Use in Pregnancy and Lactation:
The use of Viread may be
considered during pregnancy. Viread should not be used during breast
feeding.

Drug Interactions:

Viread has a low potential for CYP450 mediated interactions with other
medicinal products. Viread should not be administered concomitantly with
other medicinal products containing tenofovir disoproxil fumarate or
adefovir dipivoxil, nephrotoxic agents or medicinal products that reduce
renal function or compete for active tubular secretion. Monitor renal
function if Viread administered with tacrolimus. Co-administration with
didanosine is not recommended as it may result in a 40-60% increase in
systemic exposure to didanosine which may increase the risk of
didanosine-related adverse events. Co-administration with 400 mg daily
didanosine has been associated with significant decreases in CD4 cell
counts. A reduced dose of 250 mg didanosine administered with Viread has
been associated with reports of high rates of virological failure.
Co-administration with lopinavir/ritonavir; 30% increase in tenofovir
AUC. Co-administration with atazanavir/ritonavir decreased atazanavir
concentrations, but increased exposure to tenofovir. Higher tenofovir
concentrations could potentiate tenofovir associated adverse events
including renal disorders. Food has been shown to enhance the
bioavailability of Viread.

Gilead Sciences is a biopharmaceutical company that discovers, develops
and commercializes innovative therapeutics in areas of unmet medical
need. The company’s mission is to advance the care of patients suffering
from life-threatening diseases. Gilead has operations in more than 30
countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, that
are subject to risks, uncertainties and other factors, including the
risk that the European Commission or other regulatory agencies,
including the FDA, may not approve TAF for the treatment of chronic
hepatitis B and that any marketing approvals, if granted, may have
significant limitations on its use. As a result, Gilead may not be able
to successfully commercialize TAF for chronic hepatitis B. These risks,
uncertainties and other factors could cause actual results to differ
materially from those referred to in the forward-looking statements. The
reader is cautioned not to rely on these forward-looking statements.
These and other risks are described in detail in Gilead’s Annual Report
on Form 10-K for the year ended December 31, 2015, as filed with the
U.S. Securities and Exchange Commission. All forward-looking statements
are based on information currently available to Gilead, and Gilead
assumes no obligation to update any such forward-looking statements.